tbuckley/cabot-search huggingface dataset:
Misguided model of human behavior: Comment on C. H. Burt: “Challenging the utility of polygenic scores for social science…”
Authors: Ken Richardson
Journal: Behavioral and Brain Sciences (2023)

Abstract This commentary emphasizes two problem areas mentioned by Burt. First, that within-family designs do not eradicate stratification confounds. Second, that the linear/additive model of genetic causes of form and variation is not supported by recent progress in molecular biology. It concludes with an appeal for a (biologically and psychologically) more realistic model of such causes.
Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Caroline E. Gleason, Mark A. Dickson, Mary E. Klein (Dooley), Cristina R. Antonescu, Rodrigo Gularte-Mérida, Marimar Benitez, Juliana I. Delgado, Raghu P. Kataru, Mark Wei Yi Tan, Martina Bradic, Travis E. Adamson, Kenneth Seier, Allison L. Richards, Marta Palafox, Eric Chan, Sandra P. D'Angelo, Mrinal M. Gounder, Mary Louise Keohan, Ciara M. Kelly, Ping Chi, Sujana Movva, Jonathan Landa, Aimee M. Crago, Mark T.A. Donoghue, Li-Xuan Qin, Violetta Serra, Mesruh Turkekul, Afsar Barlas, Daniel M. Firester, Katia Manova-Todorova, Babak J. Mehrara, Marta Kovatcheva, Nguan Soon Tan, Samuel Singer, William D. Tap, Andrew Koff
Journal: Clinical Cancer Research (2023)

Abstract Purpose: We conducted research on CDK4/6 inhibitors (CDK4/6i) simultaneously in the preclinical and clinical spaces to gain a deeper understanding of how senescence influences tumor growth in humans. Patients and Methods: We coordinated a first-in-kind phase II clinical trial of the CDK4/6i abemaciclib for patients with progressive dedifferentiated liposarcoma (DDLS) with cellular studies interrogating the molecular basis of geroconversion. Results: Thirty patients with progressing DDLS enrolled and were treated with 200 mg of abemaciclib twice daily. The median progression-free survival was 33 weeks at the time of the data lock, with 23 of 30 progression-free at 12 weeks (76.7%, two-sided 95% CI, 57.7%–90.1%). No new safety signals were identified. Concurrent preclinical work in liposarcoma cell lines identified ANGPTL4 as a necessary late regulator of geroconversion, the pathway from reversible cell-cycle exit to a stably arrested inflammation-provoking senescent cell. Using this insight, we were able to identify patients in which abemaciclib induced tumor cell senescence. Senescence correlated with increased leukocyte infiltration, primarily CD4-positive cells, within a month of therapy. However, those individuals with both senescence and increased TILs were also more likely to acquire resistance later in therapy. These suggest that combining senolytics with abemaciclib in a subset of patients may improve the duration of response. Conclusions: Abemaciclib was well tolerated and showed promising activity in DDLS. The discovery of ANGPTL4 as a late regulator of geroconversion helped to define how CDK4/6i-induced cellular senescence modulates the immune tumor microenvironment and contributes to both positive and negative clinical outcomes. See related commentary by Weiss et al., p. 649
Sustainability of the Bright STAR Diagnostic Stewardship Program to Reduce Blood Culture Rates Among Critically Ill Children
Authors: Charlotte Z. Woods-Hill, Danielle W. Koontz, Elizabeth A. Colantuoni, Shaoming Xiao, Anping Xie, Marlene R. Miller, Aaron M. Milstone
Journal: JAMA Pediatrics (2023)

This quality improvement study evaluates whether pediatric intensive care units sustained reduced blood culture rates after participation in the Bright STAR collaborative from 2017 to 2020.
Use of Tenofovir Alafenamide Fumarate for HIV Pre-Exposure Prophylaxis and Incidence of Hypertension and Initiation of Statins
Authors: Adovich S. Rivera, Katherine J. Pak, Matthew T. Mefford, Rulin C. Hechter
Journal: JAMA Network Open (2023)

Pre-exposure prophylaxis (PrEP) is an important tool for preventing HIV infection. However, PrEP's impact on cardiometabolic health is understudied.To examine the risk of incident hypertension and statin initiation among adult (age ≥18 years) health plan members starting PrEP with tenofovir alafenamide fumarate (TAF) compared with propensity score-matched adults taking tenofovir disoproxil fumarate (TDF).This retrospective cohort study used electronic health records (EHRs) from Kaiser Permanente Southern California. Adult members starting PrEP in Kaiser Permanente Southern California between October 2019 and May 2022 were included. Propensity score matching with multiple imputation (50 matched data sets) was conducted to generate 1 TAF:4 TDF matched data sets with balanced baseline covariates.PrEP initiation with either TAF or TDF during the study period.Incident hypertension and statin initiation within 2 years of PrEP initiation were ascertained through blood pressure and outpatient pharmacy records, respectively. Risk differences and odds ratios (ORs) were estimated using logistic regression and g-computation.A total of 6824 eligible individuals were identified (mean [SD] age, 33.9 [10.3] years; 6618 [97%] male). This pool was used to generate 2 cohorts without baseline hypertension or statin use for matching (hypertension: n = 5523; statin: n = 6149) In both cohorts, those starting PrEP with TAF were older and were more likely to be non-Hispanic White compared with those starting with TDF. In matched analysis adjusting for baseline covariates, TAF use was associated with elevated risk of incident hypertension (TAF: n = 371; risk difference, 0.81 [95% CI, 0.12-1.50]; OR, 1.64 [95% CI, 1.05-2.56]). TAF use was also associated with elevated risk of statin initiation (TAF: n = 382; risk difference, 0.85 [95% CI, 0.37-1.33]; OR, 2.33 [95% CI, 1.41-3.85]). Subgroup analyses restricted to individuals 40 years and older at PrEP initiation showed similar results with larger risk difference in statin initiation (risk difference, 4.24 [95% CI, 1.82-6.26]; OR, 3.05 [95% CI, 1.64-5.67]).In this study of people taking PrEP, TAF use was found to be associated with higher incident hypertension and statin initiation compared with TDF use, especially in those 40 years or older. Continued monitoring of blood pressure and lipids for TAF users is warranted.
Machine-Made Empathy? Why Medicine Still Needs Humans
Authors: Angelo Cadiente, Jamie Chen, Bryan Pilkington
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Automated Opt-Out vs Opt-In Patient Outreach Strategies for Breast Cancer Screening
Authors: Leah M. Marcotte, Stefanie Deeds, Chelle Wheat, Eric Gunnink, Kristen Gray, Jorge Rojas, Carolyn Finch, Karin Nelson, Ashok Reddy
Journal: JAMA Internal Medicine (2023)

Optimal strategies for population-based outreach for breast cancer screening remain unknown.
Social scientists would do well to steer clear of polygenic scores
Authors: David Curtis
Journal: Behavioral and Brain Sciences (2023)

Abstract The problems with polygenic scores (PGSs) have been understated. The fact that they are ancestry-specific means that biases related to sociodemographic factors would be impossible to avoid. Additionally, the requirement to obtain DNA would have profound impacts on study design and required resources, as well as likely introducing recruitment bias. PGSs are unhelpful for social science research.
The social stratification of population as a mechanism of downward causation
Authors: Emily Klancher Merchant
Journal: Behavioral and Brain Sciences (2023)

Abstract This commentary expands on Burt's concept of downward causation to include any association between genomic variants and a given outcome that is forged through social practices rather than biochemical pathways. It proposes the social stratification of population, through which endogamy over a period of generations produces allele frequency differences between socioeconomic strata, as a mechanism of downward causation.
Often wrong, sometimes useful: Including polygenic scores in social science research
Authors: Jason Fletcher
Journal: Behavioral and Brain Sciences (2023)

Abstract This commentary seeks to briefly outline a clear-eyed middle ground between Burt's claims that the inclusion of polygenic scores (PGSs) is essentially useless for social science and proponents' vast overstatements and over-interpretations of these scores. Current practice of including PGSs in social science is often wrong but sometimes useful.
<i>SETD2</i> Deficiency Confers Sensitivity to Dual Inhibition of DNA Methylation and PARP in Kidney Cancer
Authors: Xinyi Zhou, Yohei Sekino, Hong-Tao Li, Guanghou Fu, Zhi Yang, Shuqing Zhao, Hemant Gujar, Xiongbing Zu, Daniel J. Weisenberger, Inderbir S. Gill, Varsha Tulpule, Anishka D’souza, David I. Quinn, Bo Han, Gangning Liang
Journal: Cancer Research (2023)

Abstract SETD2 deficiency alters the epigenetic landscape by causing depletion of H3K36me3 and plays an important role in diverse forms of cancer, most notably in aggressive and metastatic clear-cell renal cell carcinomas (ccRCC). Development of an effective treatment scheme targeting SETD2-compromised cancer is urgently needed. Considering that SETD2 is involved in DNA methylation and DNA repair, a combination treatment approach using DNA hypomethylating agents (HMA) and PARP inhibitors (PARPi) could have strong antitumor activity in SETD2-deficient kidney cancer. We tested the effects of the DNA HMA 5-aza-2′-dexoxydytidine (DAC), the PARPi talazoparib (BMN-673), and both in combination in human ccRCC models with or without SETD2 deficiency. The combination treatment of DAC and BMN-673 synergistically increased cytotoxicity in vitro in SETD2-deficient ccRCC cell lines but not in SETD2-proficient cell lines. DAC and BMN-673 led to apoptotic induction, increased DNA damage, insufficient DNA damage repair, and increased genomic instability. Furthermore, the combination treatment elevated immune responses, upregulated STING, and enhanced viral mimicry by activating transposable elements. Finally, the combination effectively suppressed the growth of SETD2-deficient ccRCC in in vivo mouse models. Together, these findings indicate that combining HMA and PARPi is a promising potential therapeutic strategy for treating SETD2-compromised ccRCC. Significance: SETD2 deficiency creates a vulnerable epigenetic status that is targetable using a DNA hypomethylating agent and PARP inhibitor combination to suppress renal cell carcinoma, identifying a precision medicine–based approach for SETD2-compromised cancers.
Midline Compared With Peripheral Intravenous Catheters for Therapy of 4 Days or Longer in Pediatric Patients
Authors: Tricia M. Kleidon, Victoria Gibson, Paula Cattanach, Jessica Schults, Ruth H. Royle, Robert S. Ware, Nicole Marsh, Colleen Pitt, Anna Dean, Joshua Byrnes, Claire M. Rickard, Amanda J. Ullman
Journal: JAMA Pediatrics (2023)

Peripheral intravenous catheters (PIVCs) frequently fail during treatment causing therapy interruption, pain, recatheterization, and additional health care costs. Midline catheters (MCs) may improve functional dwell time and reduce failure compared with traditional PIVCs.
Retuning Mitochondrial Apoptosis/Mitophagy Balance via SIRT3‐Energized and Microenvironment‐Modulated Hydrogel Microspheres to Impede Osteoarthritis
Authors: Xiaowei Xia, Yang Liu, Yingjie Lu, Junlin Liu, Yaoge Deng, Yubin Wu, Mingzhuang Hou, Fan He, Huilin Yang, Yong Xu, Yijian Zhang, Xuesong Zhu
Journal: Advanced Healthcare Materials (2023)

Full-range therapeutic regimens for osteoarthritis (OA) should consider organs (joints)-tissues (cartilage)-cells (chondrocytes)-organelles cascade, of which the subcellular mitochondria dominate eukaryotic cells' fate, and thus causally influence OA progression. However, the dynamic regulation of mitochondrial rise and demise in impaired chondrocytes and the exact role of mitochondrial metronome sirtuins 3 (SIRT3) is not clarified. Herein, chondrocytes are treated with SIRT3 natural agonist dihydromyricetin (DMY) or chemical antagonist 3-TYP, respectively, to demonstrate the positive action of SIRT3 on preserving cartilage extracellular matrix (ECM). Molecular mechanical investigations disclose that SIRT3-induced chondroprotection depended on the repression of mitochondrial apoptosis (mtApoptosis) and the activation of mitophagy. Inspired by the high-level matrix proteinases and reactive oxygen species (ROS) in the OA environment, by anchoring gelatin methacrylate (GelMA) and benzenediboronic acid (PBA) to hyaluronic acid methacrylate (HAMA) with microfluidic technology, a dual-responsive hydrogel microsphere laden with DMY is tactfully fabricated and named as DMY@HAMA-GelMA-PBA (DMY@HGP). In vivo injection of DMY@HGP ameliorated cartilage abrasion and subchondral bone sclerosis, as well as promoted motor function recovery in post-traumatic OA (PTOA) model via recouping endogenous mtApoptosis and mitophagy balance. Overall, this study unveils a novel mitochondrial dynamic-oriented strategy, holding great promise for the precision treatment of OA.
Antibody neutralisation of emerging SARS-CoV-2 subvariants: EG.5.1 and XBC.1.6
Authors: Qian Wang, Yicheng Guo, Richard M Zhang, Jerren Ho, Hiroshi Mohri, Riccardo Valdez, David M Manthei, Aubree Gordon, Lihong Liu, David D Ho
Journal: The Lancet Infectious Diseases (2023)
Transmission dynamics and effect of control measures on the 2022 outbreak of mpox among gay, bisexual, and other men who have sex with men in England: a mathematical modelling study
Authors: Xu-Sheng Zhang, Sema Mandal, Hamish Mohammed, Charlie Turner, Isaac Florence, Josephine Walker, Siwaporn Niyomsri, Gayatri Amirthalingam, Mary Ramsay, Andre Charlett, Peter Vickerman
Journal: The Lancet Infectious Diseases (2023)

The 2022 global outbreak of mpox (formerly known as monkeypox) spread primarily among gay, bisexual, and other men who have sex with men (GBMSM), with the initial cluster being identified in England in May, 2022. Understanding its epidemiological characteristics and the reasons for its downturn in July, 2022, will help to control future outbreaks.We collated data for all diagnosed mpox cases (3621) from England from May 1, 2022, to Nov 16, 2022. Data from 75 individuals with mpox allowed estimation of the incubation period, while data from 121 case-contact pairs were used to estimate the serial interval. Six methods, including a structured dynamic compartmental transmission model, were used to estimate the basic reproduction number (R0). The structured model assumed all male individuals with mpox were GBMSM, who were then stratified into subgroups for those at low risk and high risk for mpox. This best fitting model was used to estimate the reduction in transmissibility, and the effective infectious period (before isolating), that resulted in the outbreak downturn, and the effect of vaccination initiated from June 27, 2022. Bayesian methods were used for parameter estimation and model calibration.Most cases occurred in men (3544 of 3621, 97·9%). The median incubation period for mpox was 6·90 days (95% credible interval [CrI] 4·08-20·21), and the serial interval was 8·82 days (5·22-25·81). R0 estimates ranged from 1·41 to 2·17. The structured transmission model estimated that 83·8% of infections (95% CrI 83·5-85·3) resulted from sexual partnerships with GBMSM individuals at high risk of mpox. The outbreak downturn probably resulted from a 44·5% reduction in the sexual partner rate among all GBMSM (24·9-55·8) and 20·0% reduction in the effective infectious period (4·1-33·9), preventing 165 896 infections (115 584-217 730). Vaccination marginally increased the number of infections prevented (166 081, 115 745-217 947), but minimised a resurgence in cases from January, 2023, and could have averted four times more infections if initiated earlier. Our findings were sensitive to assumptions regarding the vaccine's effectiveness and the GBMSM subgroup at high risk of mpox.The mpox outbreak in England probably resulted from high sexual partner rates among some GBMSM, with reductions in partner rates reversing the outbreak, and with vaccination minimising future outbreaks.National Institute for Health Research (UK).
Self‐Emulsifying Drug Delivery Systems (SEDDS) Containing Reverse Micelles: Advanced Oral Formulations for Therapeutic Peptides
Authors: Arne Matteo Jörgensen, Christian Steinbring, Daniel Stengel, Dennis To, Pascal Schmid, Andreas Bernkop‐Schnürch
Journal: Advanced Healthcare Materials (2023)

Alternative methods to hydrophobic ion pairing for the formation of lipophilic complexes of peptide drugs to incorporate them in lipid-based nanocarriers such as self-emulsifying drug delivery systems (SEDDS) for oral administration are highly on demand. Such an alternative might be reverse micelles. Within this study, SEDDS containing dry reverse micelles (dRMs
Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial
Authors: S Lot Aronson, Marta Lopez-Yurda, Simone N Koole, Jules H Schagen van Leeuwen, Hendrik W R Schreuder, Ralph H M Hermans, Ignace H J T de Hingh, Mignon D J M van Gent, Henriëtte J G Arts, Maaike A P C van Ham, Peter A van Dam, Peter Vuylsteke, Arend G J Aalbers, Victor J Verwaal, Koen K Van de Vijver, Neil K Aaronson, Gabe S Sonke, Willemien J van Driel
Journal: The Lancet Oncology (2023)
Chronotype, Unhealthy Lifestyle, and Diabetes Risk in Middle-Aged U.S. Women
Authors: Sina Kianersi, Yue Liu, Marta Guasch-Ferré, Susan Redline, Eva Schernhammer, Qi Sun, Tianyi Huang
Journal: Annals of Internal Medicine (2023)

Evening chronotype may promote adherence to an unhealthy lifestyle and increase type 2 diabetes risk.
Travel Medicine
Authors: Robert J. Rolfe, Edward T. Ryan, Regina C. LaRocque
Journal: Annals of Internal Medicine (2023)

International travel can cause new illness or exacerbate existing conditions. Because primary care providers are frequent sources of health advice to travelers, they should be familiar with destination-specific disease risks, be knowledgeable about travel and routine vaccines, be prepared to prescribe chemoprophylaxis and self-treatment regimens, and be aware of travel medicine resources. Primary care providers should recognize travelers who would benefit from referral to a specialized travel clinic for evaluation. Those requiring yellow fever vaccination, immunocompromised hosts, pregnant persons, persons with multiple comorbid conditions, or travelers with complex itineraries may warrant specialty referral.
Annals Graphic Medicine - Diagnostic Funnel
Authors: Sujal Manohar
Journal: Annals of Internal Medicine (2023)

Web Exclusives12 September 2023Annals Graphic Medicine - Diagnostic FunnelFREESujal Manohar, BS, BASujal Manohar, BS, BABaylor College of Medicine, Houston, Texas (S.M.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0060 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Author, Article, and Disclosure InformationAuthors: Sujal Manohar, BS, BAAffiliations: Baylor College of Medicine, Houston, Texas (S.M.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0060.Author/Illustrator Information: Sujal Manohar, BS, BA, is a third-year medical student at Baylor College of Medicine (e-mail, sujal.manohar@bcm.edu). Her creative work can be viewed at sujalmanohar.com.This article was published at Annals.org on 12 September 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics September 2023Volume 176, Issue 9 ePublished: 12 September 2023 Issue Published: September 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Current insights and emerging trends in early-onset type 2 diabetes
Authors: Shivani Misra, Calvin Ke, Shylaja Srinivasan, Alpesh Goyal, Moffat J Nyriyenda, Jose C Florez, Kamlesh Khunti, Dianna J Magliano, Andrea Luk
Journal: The Lancet Diabetes & Endocrinology (2023)
20-Year Experience With Repair of Pulmonary Atresia or Stenosis and Major Aortopulmonary Collateral Arteries
Authors: Doff B. McElhinney, Ritu Asija, Yulin Zhang, Ayush Jaggi, Jennifer Shek, Lynn F. Peng, M. Gail Boltz, Michael Ma, Elisabeth Martin, Frank L. Hanley
Journal: Journal of the American College of Cardiology (2023)
Association of Coronary Artery Calcium Detected by Routine Ungated CT Imaging With Cardiovascular Outcomes
Authors: Allison W. Peng, Ramzi Dudum, Sneha S. Jain, David J. Maron, Bhavik N. Patel, Nishith Khandwala, David Eng, Akshay S. Chaudhari, Alexander T. Sandhu, Fatima Rodriguez
Journal: Journal of the American College of Cardiology (2023)
Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas
Authors: Karin Hrovatin, Aimée Bastidas-Ponce, Mostafa Bakhti, Luke Zappia, Maren Büttner, Ciro Salinno, Michael Sterr, Anika Böttcher, Adriana Migliorini, Heiko Lickert, Fabian J. Theis
Journal: Nature Metabolism (2023)

Although multiple pancreatic islet single-cell RNA-sequencing (scRNA-seq) datasets have been generated, a consensus on pancreatic cell states in development, homeostasis and diabetes as well as the value of preclinical animal models is missing. Here, we present an scRNA-seq cross-condition mouse islet atlas (MIA), a curated resource for interactive exploration and computational querying. We integrate over 300,000 cells from nine scRNA-seq datasets consisting of 56 samples, varying in age, sex and diabetes models, including an autoimmune type 1 diabetes model (NOD), a glucotoxicity/lipotoxicity type 2 diabetes model (db/db) and a chemical streptozotocin β-cell ablation model. The β-cell landscape of MIA reveals new cell states during disease progression and cross-publication differences between previously suggested marker genes. We show that β-cells in the streptozotocin model transcriptionally correlate with those in human type 2 diabetes and mouse db/db models, but are less similar to human type 1 diabetes and mouse NOD β-cells. We also report pathways that are shared between β-cells in immature, aged and diabetes models. MIA enables a comprehensive analysis of β-cell responses to different stressors, providing a roadmap for the understanding of β-cell plasticity, compensation and demise.
Survival After Cardiac Transplantation in Adults With Single-Ventricle Congenital Heart Disease
Authors: Syed Shahyan Bakhtiyar, Sara Sakowitz, Konmal Ali, Nikhil L. Chervu, Arjun Verma, Ming-Sing Si, David D’Alessandro, Peyman Benharash
Journal: Journal of the American College of Cardiology (2023)